A lot has happened since the last time I reviewed the health benefits
of selenium in this column. Unfortunately for them, the average person still
hasn't even heard of the trace mineral selenium. Fortunately, most nutritionally
oriented health food advocates are aware of much about selenium. This review
will cover many of the important findings since "Selenium Update"
and "Selenium As Food and Medicine."

Background
Selenium is an essential trace element for humans and other animals. Selenium
was named after the moon goddess, Selene, by the Swedish chemist Jons Jakob
Berzelius in 1817. Dr. Klaus Schwarz established selenium as an essential
nutrient for animals in 1957, but the first selenium function in humans
wasn't discovered until 1973. [1] Dr. John Rotruck and his colleagues at
the University of Wisconsin demonstrated that selenium was incorporated
into molecules of an enzyme called glutathione peroxidase (GPX). This vital
enzyme protects red blood cells, cell membranes and sub-cellular components
against undesirable reactions with soluble peroxides.

The discovery of GPX opened the door to our understanding of how selenium
is protective against cancer, heart disease, arthritis and accelerated aging.
Now more scientific excitement is being generated with the recent finding
that selenium is also a vital component of other mammalian enzymes.

Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPX) protects membranes
against peroxides already bound to membrane surfaces. [2] PHGPX blocks formation
of the extremely harmful alkoxyl radical and inhibits peroxidative chain
branching. This activity is even of more importance in the prevention of
cancer, heart disease and accelerated aging.

Now addition pathways in which selenium is involved in health are being
uncovered. Selenium is a component of the enzyme that is needed to produce
the most active thyroid hormone. Sub-optimal amounts of selenium impair
thyroid hormone function and thus affects many body functions.

Biochemists are now studying several other selenium proteins and have classified
them into four main categories. [3]

Cancer
First there were animal studies that showed that selenium protected against
chemicals and ultraviolet energy that cause cancer. [4-7] These laboratory
findings were also supported by epidemiological studies (population surveys),
and now large scale clinical studies are being sponsored by the U. S. government.
[8-15]

Heart Disease
Epidemiological studies have shown that persons with low-selenium diets
have two-to-three times greater risk of heart disease than those eating
selenium rich diets. [16] In a clinical study, patients with blockage of
all three coronary arteries had low blood selenium levels, while those with
high blood selenium levels were healthy and free of coronary heart disease.
[17] Strikingly, those with one diseased coronary artery had the next highest
blood selenium levels, and those with two blocked coronary arteries had
the second lowest blood selenium levels.

Clearly, the antioxidant protection of the selenium-containing enzymes,
GPX and PHGPX, protect the arteries and cholesterol-carrying lipoproteins
against the damage that leads to heart disease.

Arthritis
Arthritic inflammation is produced by certain hormone-like compounds called
prostaglandins. Selenium is involved in controlling these specific prostaglandins
by controlling the free-radical damage that stimulates their production.

Norwegian physicians had noted that arthritis patients tended to have low
blood selenium levels. When their arthritis ***patients were given selenium
supplements, they dramatically** improved. [18] A Danish study has confirmed
the Norwegian study. [19]

Hypothyroidism
Selenium is a component of the enzyme that is needed to produce the thyroid
hormone triiodothyronine (T3). T3 is the preponderant metabolic thyroid
hormone. The selenium-containing enzyme, iodothyronine deiodinase, converts
the prohormone thyroxine (T4) into T3. [20]

This explains the observation that selenium deficiency impairs thyroid hormone
function. Impaired thyroid hormone function is called hypothyroidism and
affects many body functions.

Other Areas of Study
The role of selenium in possibly slowing the aging process has been under
laboratory study for more than 25 years, but there are no known plans for
clinical studies at this time. [21-3]

Studies also indicate that selenium protects against cataracts and skin
damage, and is important to prostate function. A patent has even been applied
for that claims selenium significantly helps Alzheimer's patients. [24]
Several books describe the many beneficial roles of selenium in health.
[23, 25-6]

Forms of Selenium Supplements
The most efficacious and safest forms to supplement our diet with selenium
is not the inorganic salt form, but the organic forms, selenium yeast and
selenomethionine.

Selenium Yeast
Selenium yeast is produced when selenium is naturally incorporated into
the protein of growing yeast under optimum conditions. The resultant yeast
has a high concentration of the selenium-containing proteins, selenomethionine
and selenocysteine. Products that are created by mixing yeast with inorganic
selenium are still merely inorganic selenium products.

Beneficial nutritional brewer's yeast (Saccharomyces cerevisiae) does not
contribute to yeast infections such as Candida albicans. Food yeasts are
not infectious. Nutritional yeasts are not live yeast cells. If they were,
live yeast cells would actually compete with one another and nutritional
yeasts would actually suppress Candida albicans yeast growth. However, selenium
yeast is carefully dried after it is grown. This kills the yeast and it
can no longer grow or multiply. Brewer's yeast has been a staple of the
health food industry since its inception. The famous health teachers all
advocated brewer's yeast in one form or another because it is rich in
the B-complex vitamins and other nutrients that were not available as purified
nutrients in the past. Brewer's yeast still may contain nutrients that we
have yet to discover.

Selenium yeast was found to out-perform inorganic selenium in increasing
the amount of selenium in the milk of lactating mothers and the blood of
their infants. The researchers concluded, "Selenium yeast was safe
and more effective than selenite." [27]

In another test, 150 micrograms daily of selenium as selenium yeast was
effective in raising blood selenium levels of healthy adults, whereas the
same amount of inorganic yeast failed to raise blood selenium levels. [28]
Dr. Gerhard Schrauzer of the University of California-San Diego concludes
"since a ten-fold lower oral dosage of organic selenium produced a
two-fold greater increase in selenium levels in the blood, organically-bound
selenium is at least twenty-fold more effective in providing the body with
the trace element." [29]

Selenomethionine
Selenomethionine is a purified selenium-containing amino acid. There is
no yeast in selenomethionine. Selenomethionine is a naturally occurring
component of food. Selenomethionine is similar to the essential amino
acid methionine but with an atom of selenium instead of an atom of sulfur.

The form of selenomethionine that the body can use is L-selenomethionine.
L-selenomethionine is better absorbed and better incorporated into body
components than any other known form of selenium. Experiments
comparing inorganic selenium with DL-selenomethionine found that DL-selenomethionine
was not as effective as the inorganic selenium [45]. D-selenomethionine
is degraded to inorganic selenium and returned to the inorganic selenium
body pool, and thus is only one-fifth as bioavailable as L-selenomethionine.
[31]

I have been using various forms of selenium in my animal studies for thirty
years and find that the selenium-containing amino acids (selenomethionine
and selenocysteine) and the methylated selenides are far superior to the
inorganic forms of selenium (selenite and selenate) in terms of overall
health, longevity and freedom from cancer.

In studies in New Zealand, it was found that selenomethionine was at least
75 percent bioavailable, compared to 59 percent for sodium selenite. Blood
selenium levels rose more quickly and didn't plateau as early with selenomethionine
than with sodium selenite. [30-32]

In a Finnish study, again selenomethionine raised blood selenium levels
higher and remained in the blood longer than inorganic selenium. [33] In
a later Finnish study, it was found that as much as 3,500 micrograms of
inorganic selenium had to be given to raise their blood selenium levels
to match that of typical Americans. The long-term safety of such a high
dose of inorganic selenium is not known.

In 1984, a MIT study determined that organic forms of selenium are able
to increase the body pool size about 70 percent more effectively than inorganic
selenite. [34]

Dr. P. Whanger of Oregon State University has spent several years studying
the effectiveness of several forms of selenium supplements. He has published
several papers on this subject through the years utilizing various laboratory
animals and human clinical trials. His latest research was published in
the MArch issue of the American Journal of Clinical Nutrition. Some of his
findings include, "The selenium concentrations in all blood fractions
increased at a faster rate (two- to three- fold) in women taking selenomethionine
than in those taking selenate...About 95 percent of the selenium was associated
with hemoglobin in women taking selenomethionine - interestingly, most of
the GPX activity was also associated with hemoglobin...This suggests that
selenium increases in these fractions only when selenomethionine is supplied
and that the increase is restricted to hemoglobin." [35]

Selenoproteins and selenium transport
We now know that several selenium-containing proteins exist, so selenium
is essential in more ways than we knew in 1973. Earlier I discussed two
new enzymes, PHGPX and iodothyronine deiodinase. Enzymes are proteins. But
there are many other selenium-containing proteins, including muscle proteins
and other selenium-containing enzymes. Dr. Roger Sunde of the University
of Missouri-Columbia has classified selenoproteins into four distinct groups.
[3] Table 1 lists the proteins of the selenium ion-specific selenoproteins,
the selenomethionine-specific proteins, the selenocysteine-specific proteins
and the selenium binding proteins.

Selenomethionine can furnish the required form of selenium for all four,
whereas inorganic selenium has to be converted into selenomethionine or
selenocysteine to be incorporated into two of the classes of selenoproteins.
Notice in figure 1 that selenomethionine is incorporated directly into the
selenomethionine-specific proteins. Selenomethionine can also be converted
in the body into selenocysteine to form the selenocysteine-specific proteins.
Also, selenomethionine can be catabolized into selenium ions to form the
selenium ion-specific selenoproteins. It is easier for selenomethionine
to provide selenium ions than it is for inorganic selenium to be converted
into selenomethionine.

The transport protein for selenium ions is selenoprotein-P.

Inorganic selenium
As discussed earlier, inorganic selenium forms (selenate and selenite) are
not as well absorbed as organic selenium-containing amino acids (selenomethionine
and selenocysteine). However, inorganic selenium dissolved in the drinking
water of laboratory animals has been effective in preventing various cancers.
However, this is not how humans normally get most of their selenium; it
is in their food, not their water.

Inorganic selenium, at low doses, is better than no selenium at all. However,
larger doses of inorganic selenium has an oxidative effect that increases
undesirable lipofuscin production. [36] The selenium in inorganic selenite
is in the plus four valance state which is very oxidative. The selenium
of selenomethionine is in the minus two valance state. The lipofuscin accumulation
in the liver can be accounted for by the fact that in order for selenium
to go from the inorganic plus four valance state to the plus minus valance
state, six electrons must be obtained from liver cells. The safety of inorganic
selenium is about one-third that of selenomethionine. [37]

Inorganic sources of selenium do not find their way to muscle protein to
an appreciable extent. If laboratory animals are fed selenomethionine, selenium
soon increases in all organs, muscles, GPX and hemoglobin. When inorganic
selenium is fed to animals, it accumulates in the liver, kidneys and GPX.

Inorganic selenium reacts spontaneously with sulphydryl groups to form selenotrisulfides.
This can severely disrupt the structure of proteins. Inorganic selenium
reacts with the sulfhydryl groups of glutathione to form selenopersulfide
and free selenide. Inorganic selenium, due to its free-radical promoting
oxidative nature, is mutagenic and has caused cataracts at high doses in
mice. [44] In contrast, selenium-containing amino acids are stable, less
toxic, and do not have mutagenic or oxidizing activity.

Synergism With Vitamins C and E
Vitamin C increases the absorption of selenomethionine and organic selenium-containing
yeasts. Two differing reports exist concerning vitamin C and inorganic selenite.
[38,39] One report shows that vitamin C inhibits inorganic selenium absorption,
while the other shows that vitamin C enhances inorganic selenium absorption.
The confusion may result from the fact that if vitamin C mixes with inorganic
selenium in the food, the inorganic selenium is reduced to insoluble and
biologically inert metallic selenium.

Vitamin E is a partner with selenium in protecting body components against
oxidative free radicals. Both vitamin E and selenium have their own specific
modes of stopping free radicals, plus they have common modes. The two are
"synergistic" which means that the activity of both together is
greater than the sums of the activity of each by itself. It's a case
of nutritionally adding one plus one and getting more than three. Vitamin
E and selenium are a powerful combination and the body needs both together.

Daily intake and safety
In 1980, the National Academy of Sciences stated that a safe and effective
range for selenium intake is 50 to 200 micrograms. In 1989, a daily
RDA of 75 micrograms for men and 55 micrograms for women was established.
The FDA has not as yet set a USRDA for selenium. Conventional supplementation
practices are to add 50 to 200 micrograms of selenium to the daily diet.

In my three-part 1986 series on selenium safety, I discussed that many natural
diets contained more than 600 micrograms of selenium daily. [40-42] In Northern
Greenland, many residents consume about 1,300 micrograms of selenium daily.
And, in China, some residents were found who took 1,000 micrograms of selenium
daily when they found out that it protected them from certain selenium-deficiency
diseases (including Keshan disease) endemic to their area. They developed
thickened fingernails and a garlic-like breath. Now we have a report that
a woman took 2,400,000 micrograms of selenium daily for seventy-five days
with only mild and reversible side effects. [43] This is 12,000 times the
recommended upper limit for supplementation for healthy people.

Keep in mind that everything -- even oxygen and water -- is toxic at some
level. It is the dose that makes the poison. The amount of selenium supplement
that is safe and effective is the old recommended daily range of 50 to 200
micrograms daily. Yet, we continue to read the foolishness that the cancer-protecting
dose is toxic. That nonsense is a disservice to everyone.

Conclusion
We still have more to learn about selenium than we already know, but it
is clear that selenium is extremely important to our health. It's a shame
that more people don't know about selenium. In a future article on selenium,
I will interview Dr. Gerhard Schrauzer of the University of California-San
Diego. Perhaps Dr. Schrauzer's provocative comments will help to get the
public interested in protecting their health with selenium.

Richard A. Passwater, Ph.D. has been a research biochemist since 1959. His first areas of research was in the development of pharmaceuticals and analytical chemistry. His laboratory research led to his discovery of......more

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